DESCRIPTION: Collateral sprouting by mature, noninjured neurons is known to be dependent on neurotrophic factors in several central and peripheral sites. For example, neurotrophins facilitate cholinergic sprouting following entorhinal cortex lesions, corticospinal tract sprouting after spinal cord lesions, and hippocampal mossy fiber sprouting during kindling. In the periphery, intact sensory and sympathetic axons respond to injury of neighboring nerves by sprouting into the denervated territory. The time course of such collateral sprouting by sensory axons is enhanced by exogenous NGF and inhibited by NGF antibodies. Here, neurotrophin actions on central and peripheral sprouting of sensory axons will be studied in a model where pronase is injected into the sciatic nerve of rats. Central loss of sciatic afferents results from the death of sciatic dorsal root ganglion cells; subsequently, spared saphenous axons with or without myelin sprout into deafferented portions of the lumbar dorsal horn. Proposed studies will assess whether peripheral perineural or central intrathecal delivery of NGF or BDNF, or antibodies to NGF or BDNF, alter the timecourse or extent of saphenous nerve sprouting in the skin and dorsal horn. The extent to which peripheral sprouting predicts central sprouting will also be evaluated. In the same animals, changes in expression of high- and low-affinity receptors for NGF and BDNF will be studied to reveal possible mechanisms mediating neurotrophin actions.